(1) Field of the Invention
This invention relates to a new anthracycline antibiotic, to a method for its manufacture, to pharmaceutical compositions containing it and to methods of using said antibiotic as an antimicrobial and antitumor agent.
(2) Description of the Prior Art
There is disclosed in U.S. Pat. No. 4,039,736 the fermentation of Actinosporangium sp. ATCC 31127 to produce an antibiotic complex designated therein as bohemic acid complex and the separation of said complex into two novel anthracycline antibiotics designated musettamycin and marcellomycin. Musettamycin and marcellomycin contain the aglycone, .epsilon.-pyrromycinone, and have the structural formulae ##STR1##
By the present invention there has been discovered and isolated in substantially pure form a novel anthracycline antibiotic designated as rudolphomycin. Rudolphomycin has been found by the present inventors to be a minor bioactive component of the bohemic acid complex produced in the fermentation of Actinosporangium sp. ATCC 31127.
A number of .epsilon.-pyrromycinone glycosides have been described in the literature. Illustrative of such anthracyclines are the following:
1. Cinerubin A and cinerubin B are disclosed in U.K Pat. No. 846,130 [see also U.S. Pat. No. 3,864,480 and Keller-Schierlein et al., Antimicrobial Agents and Chemotherapy, page 68 (1970) and Chemical Abstracts, 54, 1466i (1960)]. PA1 2. Pyrromycin, an anthracycline antibiotic containing rhodosamine as the glycosidic sugar, is disclosed in Chem. Ber., 92, 1904-1909 (1959). PA1 3. Galirubin A is disclosed in Chemical Abstracts, 64, 3896g (1966) and Chemical Abstracts, 67, 90573z (1967). PA1 4. Rutilantin is described in Biochem. J., 81, 101-104 (1961).
Trypanomycin is described in Antimicrobial Agents and Chemotherapy, 1, 385-391 (1972) as having strong antiprotozoal activity. It has an aglycone similar to but not identical with .epsilon.-pyrromycinone.
The textbook Antibiotics, Volume 1, Mechanism of Action, edited by David Gottlieb and Paul D. Shaw, Springer-Verlag New York, Inc., N.Y., N.Y. (1967) at pages 190-210 contains a review by A. DiMarco entitled Daunomycin and Related Antibiotics.
Information Bulletin, No. 10, International Center of Information of Antibiotics, in collaboration with WHO, December, 1972, Belgium, reviews anthracyclines and their derivatives.